The present invention is generally related to analytical tools for the biological and chemical sciences, and in particular, provides microfluidic devices, systems, and methods for selectively transporting fluids within microfluidic channels of a microfluidic network, often using a plurality of selectively variable pressures.
Microfluidic systems are now in use for the acquisition of chemical and biological information. These microfluidic systems are often fabricated using techniques commonly associated with the semiconductor electronics industry, such as photolithography, wet chemical etching, and the like. As used herein, “microfluidic” means a system or device having channels and chambers which are at the micron or submicron scale, e.g., having at least one cross-sectional dimension in a range from about 0.1 μm to about 500 μm.
Applications for microfluidic systems are myriad. Microfluidic systems have been proposed for capillary electrophoresis, liquid chromatography, flow injection analysis, and chemical reaction and synthesis. Microfluidic systems also have wide ranging applications in rapidly assaying compounds for their effects on various chemical, and preferably, biochemical systems. These interactions include the full range of catabolic and anabolic reactions which occur in living systems, including enzymatic, binding, signaling, and other reactions.
A variety of methods have been described to effect the transport of fluids between a pair of reservoirs within a microfluidic system or device. Incorporation of mechanical micro pumps and valves within a microfluidic device has been described to move the fluids within a microfluidic channel. The use of acoustic energy to move fluid samples within a device by the effects of acoustic streaming has been proposed, along with the use of external pumps to directly force liquids through microfluidic channels.
The capabilities and use of microfluidic systems advanced significantly with the advent of electrokinetics: the use of electrical fields (and the resulting electrokinetic forces) to move fluid materials through the channels of a microfluidic system. Electrokinetic forces have the advantages of direct control, fast response, and simplicity, and allow fluid materials to be selectively moved through a complex network of channels so as to provide a wide variety of chemical and biochemical analyses. An exemplary electrokinetic system providing variable control of electro-osmotic and/or electrophoretic forces within a fluid-containing structure is described in U.S. Pat. No. 5,965,001, the full disclosure of which is incorporated herein by reference.
Despite the above-described advancements in the field of microfluidics, as with all successes, still further improvements are desirable. For example, while electrokinetic material transport systems provide many benefits in the micro-scale movement, mixing, and aliquoting of fluids, the application of electrical fields can have detrimental effects in some instances. In the case of charged reagents, electrical fields can cause electrophoretic biasing of material volumes, e.g., highly charged materials moving to the front or back of a fluid volume. Where transporting cellular material is desired, elevated electrical fields can, in some cases, result in a perforation or electroporation of the cells, which may effect their ultimate use in the system.
To mitigate the difficulties of electrokinetic systems, simplified transport systems for time domain multiplexing of reagents has been described in WO 00/45172 (assigned to the assignee of the present invention), the full disclosure of which is incorporated herein by reference. In this exemplary time domain multiplexing system, structural characteristics of channels carrying reagents can, at least in part, regulate the timing and amount of reagent additions to reactions (rather than relying solely on the specific times at which pumps are turned on and/or valves are actuated to regulate when and how much of a particular reagent is added to a reaction). While other solutions to the disadvantageous aspects of electrokinetic material transport within a microfluidic system have been described, still further alternative fluid transport mechanisms and control methodologies would be advantageous to enhance the flexibility and capabilities of known microfluidic systems.
Regardless of the mechanism used to effect movement of fluid and other materials within a microfluidic channel network, accuracy and repeatability of specific flows can be problematic. There may be variations in, for example, electroosmotic flow between two chips having similar designs, and even between different operations run on a single chip at different times. Quality control can be more challenging in light of this variability, as accurate control over microfluidic flows in applications such as high throughput screening would benefit significantly from stable and reliable assays.
In light of the above, it would be advantageous to provide improved microfluidic devices, systems, and methods for selectively transporting fluids within one or more microfluidic channels of a microfluidic network. It would be desirable if these improved transport techniques provided selective fluid movement capabilities similar to those of electrokinetic microfluidic systems, while mitigating the disadvantageous aspects of the application of electrical fields to chemical and biochemical fluids in at least some of the microfluidic channels of the network.
It would also be beneficial to provide improved devices, systems, methods and kits for enhancing the accuracy, reliability, and stability of microfluidic flows within a microfluidic network. It would be beneficial if these enhanced flow control techniques provided real-time and/or quality control feedback on the actual flows, ideally without relying on significantly increased system complexity or cost.